US8703694B2ActiveUtilityA1

Methods for increasing thermogenic adipocytes

99
Assignee: KNOPF JOHNPriority: Jun 8, 2009Filed: Feb 23, 2012Granted: Apr 22, 2014
Est. expiryJun 8, 2029(~2.9 yrs left)· nominal 20-yr term from priority
Inventors:John KnopfJasbir SeehraRavindra Kumar
A61K 31/7088A61P 3/10C12N 5/0653C07K 2319/30C12N 5/0667A61K 38/00A61P 21/00C07K 14/71C07K 16/40C12N 2501/16A61P 3/04A61P 3/00A61K 38/1796C07K 14/705A61K 38/18A61K 38/179
99
PatentIndex Score
43
Cited by
394
References
42
Claims

Abstract

In certain aspects, the present invention provides compositions and methods for increasing thermogenic adipocytes (e.g., brown adipocytes or other UCP-1 expressing adipocytes) by administering an antagonist of an ActRIIB signaling pathway. Examples of such antagonists include ActRIIB polypeptides, anti-ActRIIB antibodies, anti-myostatin antibodies, anti-GDF3 antibodies, anti-Nodal, anti-activin, and anti-GDF 11 antibodies. A variety of metabolic and other disorders may be treated by causing an increase in thermogenic adipocytes.

Claims

exact text as granted — not AI-modified
We claim: 
     
       1. A method for increasing thermogenic adipocytes in a patient in need thereof, the method comprising administering an effective amount of an antibody, or antigen binding fragment thereof, that specifically binds to and inhibits an extracellular domain of an activin type IIB [ActRIIB) protein, and wherein the inhibition of the extracellular domain of the ActRIIB protein results in increasing thermogentic adipocytes in the patient. 
     
     
       2. The method of  claim 1 , wherein the antibody, or antigen-binding fragment thereof, is monoclonal. 
     
     
       3. The method of  claim 1 , wherein the antibody, of antigen-binding fragment thereof, is chimeric. 
     
     
       4. The method  claim 1 , wherein the antibody, or antigen-binding fragment thereof, is humanized. 
     
     
       5. The method of  claim 1 , wherein the antibody, or antigen binding fragment thereof, is selected from: a single chain antibody, a bispecific antibody, a F(ab) 2  fragment, and a Fab' fragment. 
     
     
       6. The method of  claim 1 , wherein the patient has a metabolic disorder. 
     
     
       7. The method  claim 6 , wherein the patient has obesity. 
     
     
       8. The method of  claim 6 , wherein the patient has diabetes. 
     
     
       9. The method of  claim 8 , wherein the patient has type II diabetes. 
     
     
       10. The method of  claim 6 , wherein the patient has lipodystrophy. 
     
     
       11. The method of  claim 1 , wherein the patient has a muscle disorder and a metabolic disorder. 
     
     
       12. The method of  claim 11 , wherein the patient has cachexia. 
     
     
       13. The method of  claim 11 , wherein the patient has muscular dystrophy. 
     
     
       14. The method of  claim 11 , wherein the patient has HIV. 
     
     
       15. The method of  claim 1 , wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO:1. 
     
     
       16. The method of  claim 15 , wherein the antibody, or antigen-binding fragment thereof, is monoclonal. 
     
     
       17. The method of  claim 15 , wherein the antibody, of antigen-binding fragment thereof, is chimeric. 
     
     
       18. The method  claim 15 , wherein the antibody, or antigen-binding fragment thereof, is humanized. 
     
     
       19. The method of  claim 15 , wherein the antibody, or antigen binding fragment thereof, is selected from: a single chain antibody, a bispecific antibody, a F(ab) 2  fragment, and a Fab' fragment. 
     
     
       20. The method of  claim 15 , wherein the patient has a metabolic disorder. 
     
     
       21. The method  claim 20 , wherein the patient has obesity. 
     
     
       22. The method of  claim 20 , wherein the patient has diabetes. 
     
     
       23. The method of  claim 22 , wherein the patient has type II diabetes. 
     
     
       24. The method of  claim 20 , wherein the patient has lipodystrophy. 
     
     
       25. The method of  claim 15 , wherein the patient has a muscle disorder and a metabolic disorder. 
     
     
       26. The method of  claim 25 , wherein the patient has cachexia. 
     
     
       27. The method of  claim 25 , wherein the patient has muscular dystrophy. 
     
     
       28. The method of  claim 25 , wherein the patient has HIV. 
     
     
       29. The method of  claim 1 , wherein the extracellular domain consists of the amino acid sequence of SEQ ID NO:1. 
     
     
       30. The method of  claim 29 , wherein the antibody, or antigen-binding fragment thereof, is monoclonal. 
     
     
       31. The method of  claim 29 , wherein the antibody, of antigen-binding fragment thereof, is chimeric. 
     
     
       32. The method  claim 29 , wherein the antibody, or antigen-binding fragment thereof, is humanized. 
     
     
       33. The method of  claim 29 , wherein the antibody, or antigen binding fragment thereof, is selected from: a single chain antibody, a bispecific antibody, a F(ab) 2  fragment, and a Fab' fragment. 
     
     
       34. The method of  claim 29 , wherein the patient has a metabolic disorder. 
     
     
       35. The method  claim 34 , wherein the patient has obesity. 
     
     
       36. The method of  claim 34 , wherein the patient has diabetes. 
     
     
       37. The method of  claim 36 , wherein the patient has type II diabetes. 
     
     
       38. The method of  claim 34 , wherein the patient has lipodystrophy. 
     
     
       39. The method of  claim 29 , wherein the patient has a muscle disorder and a metabolic disorder. 
     
     
       40. The method of  claim 39 , wherein the patient has cachexia. 
     
     
       41. The method of  claim 39 , wherein the patient has muscular dystrophy. 
     
     
       42. The method of  claim 39 , wherein the patient has HIV.

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